The orbito-frontal cortex (OFC) has been implicated in emotional thought regulation. Specifically, the OFC is known to play a role in coordinating behavioral and cognitive responses to salient emotional stimuli and events. Further, OFC dysfunction has been observed in a number of psychiatric disorders (e.g., major depressive and anxiety disorders) characterized by intrusive negative thought processes such as rumination and worry, which may be caused by a failure to regulate emotional thoughts. However, the specific role of the OFC in the monitoring, expression, and inhibition of verbal emotional thoughts remains unexplored. Thus, the main goal of the proposed research project is to establish the functional involvement of the OFC in the recall, spontaneous generation, and inhibition of positive, negative, and neutral verbal thoughts using an fMRI activation and a brain lesion study. The functional involvement of the OFC in the expression and inhibition of verbal emotional thoughts will be investigated during a) silent cued recall of emotional and neutral words; b) generation of novel emotional and neutral words in response to a novel cue; and c) generation of novel words in response to a cue from a previously learned pair of associates (i.e., inhibition of previously learned associations). Relative increases or decreases in OFC activity and measures of reaction time and accuracy will signify functional recruitment of the OFC during the retrieval, generation, and inhibition of verbal emotional thoughts. In combination with formal didactic training, the proposed research project will satisfy this application's long-term objective to provide adequate knowledge and skills necessary for the applicant to conduct independent research that a) identifies brain mechanisms contributing to the regulation (i.e., spontaneous generation and inhibition) of emotional thoughts; b) specifies brain regions and neural circuits contributing to the over-generation and abnormal inhibition of emotional thoughts in psychiatric disorders associated with unwanted intrusive thoughts; and c) examines how stress and treatment interact with the functioning of these neural circuits to augment or diminish expression of intrusive thoughts. Investigating contributions of the OFC to the generation and control of verbal emotional thoughts will promote a better understanding of OFC function and will lay a foundation for the future examination of neural mechanisms of the etiology, symptom expression, and maintenance of psychiatric disorders characterized by intrusive thoughts. In addition, this project will attempt to outline the extent of functional deficits in the generation and inhibition of emotional thought in individuals with organic OFC damage. [unreadable] [unreadable] [unreadable]